Stem cell research may be boon to fertility clinics / Insight gleaned in lab could help couples conceive

Carl T. Hall, Chronicle Science Writer

Published
4:00 am PST, Monday, February 21, 2005

STEMCELLSIVF_001_CAG.JPG
Dr. Shehua Shen, director of the UCSF embryology lab, stands next to two of the rooms used to collect ova from donors and women seeking in vitro fertilization. One of the first areas of clinical medicine expected to get any benefit from human embryonic stem cell research may be the very same IVF clinics that provide the human embryos needed to do the research. At UCSF, for instance, stem cell researchers are deriving new colonies of stem cells on "feeder layers" of cells they take from human placentas, a technique already being used by the IVF specialists to improve odds of success in a few difficult cases of infertility. By contrast, the much touted prospect of using stem cells to cure diseases such as ALS or diabetes is a very long way off. Photo by Carlos Avila Gonzalez / The San Francisco Chronicle
Photo taken on 2/17/05 in San Francisco, CA. MANDATORY CREDIT FOR PHOTOG AND SAN FRANCISCO CHRONICLE/ -MAGS OUT less

STEMCELLSIVF_001_CAG.JPG
Dr. Shehua Shen, director of the UCSF embryology lab, stands next to two of the rooms used to collect ova from donors and women seeking in vitro fertilization. One of the first areas ... more

Photo: Carlos Avila Gonzalez

Photo: Carlos Avila Gonzalez

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STEMCELLSIVF_001_CAG.JPG
Dr. Shehua Shen, director of the UCSF embryology lab, stands next to two of the rooms used to collect ova from donors and women seeking in vitro fertilization. One of the first areas of clinical medicine expected to get any benefit from human embryonic stem cell research may be the very same IVF clinics that provide the human embryos needed to do the research. At UCSF, for instance, stem cell researchers are deriving new colonies of stem cells on "feeder layers" of cells they take from human placentas, a technique already being used by the IVF specialists to improve odds of success in a few difficult cases of infertility. By contrast, the much touted prospect of using stem cells to cure diseases such as ALS or diabetes is a very long way off. Photo by Carlos Avila Gonzalez / The San Francisco Chronicle
Photo taken on 2/17/05 in San Francisco, CA. MANDATORY CREDIT FOR PHOTOG AND SAN FRANCISCO CHRONICLE/ -MAGS OUT less

STEMCELLSIVF_001_CAG.JPG
Dr. Shehua Shen, director of the UCSF embryology lab, stands next to two of the rooms used to collect ova from donors and women seeking in vitro fertilization. One of the first areas ... more

Photo: Carlos Avila Gonzalez

Stem cell research may be boon to fertility clinics / Insight gleaned in lab could help couples conceive

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One of the first areas of clinical medicine to derive any practical benefit from human embryonic stem cell research may well be the same fertility clinics that provide the embryos used to generate the stem cells.

In vitro fertilization clinics gave rise to the stem cell field in the first place, by generating large numbers of excess human embryos being kept in frozen storage. In 1998, researchers in Wisconsin found a way to derive colonies of stem cells from a few of those embryos that had been donated for research.

Now, scientists say the burgeoning interest in stem cell research is producing insights already circling back into IVF practice.

Fertility specialists hope the stem cell work will lead to better methods of handling embryos and perhaps provide a clearer understanding of human development at this very early stage. Ultimately, this could translate into improved IVF success rates.

"If we can find the best way to grow embryos to get stem cells, and understand the best techniques to nurture them, then we can do studies to see if it might make a difference in our standard culture lines for things we are indeed going to place into patients," said Dr. David Smotrich, medical director and founder of La Jolla IVF.

Human embryonic stem cells are usually derived when the embryo is about 4 or 5 days old, having formed what is known as the "inner cell mass," a clump of stem cells whose further growth and differentiation leads to a fully formed embryo and, if implanted in the womb, a growing fetus.

Stem cells and IVF

The stem cell researchers hope to work out every step of this process in order to determine just how the all-purpose stem cells manage to turn into the particular cells that make up the human body. Their findings clearly have implications for IVF -- one reason many clinics are forming active collaborations with stem cell laboratories.

Smotrich is working with stem cell biologist Evan Snyder of the Burnham Institute, a research center located nearby in San Diego. He said the collaboration is still in the early stage and has yet to change the outcome for any of his patients trying to conceive. But he said he is increasingly optimistic.

"I am hopeful we are going to learn more and more information that will be useful in the clinic," he said.

Although IVF methods have become much more sophisticated since Louise Brown, the first IVF baby, was born in 1978, frustration is still a hallmark of the field. Many infertile couples have difficulty conceiving even after multiple tries and all the latest tricks of the trade -- sometimes for no apparent reason.

"You are dealing with a biological system whose signals we just don't understand, by and large," Snyder said.

Piecing together those signals is one of the fundamental goals of Proposition 71, the California initiative that authorized $3 billion for tax- supported stem cell research. But the improvement of IVF practices gets very little attention, paling beside the idea that stem cells can help cure Lou Gehrig's disease or allow people with damaged spinal cords to walk again.

James Battey, head of a stem cell task force for the National Institutes of Health, said the largely unheralded prospect of better IVF underscores the need to actively investigate "all kinds of stem cells," including those derived from embryos -- even though NIH grants for the embryonic cells are restricted.

"We need to be very open-minded about how these stem cells ultimately may produce a benefit," he said.

Indeed, scientists and policy-makers agree that IVF is far more likely to be the place to look for the first tangible medical benefits from the California program and others like it springing up around the country.

But they are not the sort of results likely to qualify as one of the breakthroughs touted during the Prop. 71 campaign.

"One has to suspect a lot of the first advances are going to be in the area of process," said Jeff Sheehy, a San Francisco AIDS activist who serves as a director of the Prop. 71-created California Institute for Regenerative Medicine. "The first thing that happens in something like this is you develop better tools and methods."

Stem cell laboratories often use many of the same methods as those used to help couples conceive.

"These are technical advances," Snyder said, citing examples such as finding the best ways of thawing and freezing embryos or determining which materials make the best surfaces on which to place reproductive materials in a laboratory.

Placental cells

Dr. Marcelle Cedars, director of reproductive endocrinology at UCSF, can point to one such advance already: Her UCSF colleague, Susan Fisher, has been deriving embryonic stem cell lines nourished on beds of human cells purified from placental tissue, rather than using the standard "feeder layer" of mouse cells.

Fisher worked out this technique -- one of several approaches being tried -- partly to produce stem cell lines free of contaminants picked up from contact with animal cells. Only purely human cells are likely to become ingredients in any stem cell-based treatments for human disease.

In turn, Cedars is experimenting with the placental-cell feeder layers for some of her most difficult infertility cases, replacing the standard culture media used to nourish embryos in vitro.

The culture media usually works well enough to keep an embryo in healthy condition long enough to implant. But sometimes, for unknown reasons, the embryos seem to need more help -- and the placental cells appear to be a natural alternative, generating a rich mix of nutrients while at the same time filtering out waste products.

"We use feeder layers for some of our poor-prognosis patients," Cedars said. "Just as the stem cells need a richer nutrient environment than culture media can provide, so do the embryos frequently in our laboratory. If you think about what we do in the lab, it's very artificial compared with what nature does."

Cedars is hoping close collaboration with Fisher and other stem cell biologists will translate into some truly fundamental advances over time -- recipes for "making IVF smarter" by more closely matching the natural environment in the laboratory setting.

"We've got a much more sort of finite question we're trying to solve," she said. "A lot of these other applications are far down the line -- things like curing diabetes or replacing damaged spinal cord cells."

Scientists are only beginning to glimpse all the intricate interactions that go on between the cells of the embryo and its environment. By using placental cells in the laboratory, Fisher said, researchers for the first time are able to "characterize the interactions" each step along the way.

Those findings may help shape stem cell treatments. Back in the IVF clinic, Cedars hopes to use the findings much sooner.

"You can take it one step further and apply it to the fetus in utero, into perhaps better ways to promote fetal health," she said, adding that some of the greatest frustrations in IVF occur when someone manages to become pregnant and then miscarries.

By this logic, it seems reasonable to expect more successful pregnancies through IVF as the stem cell field advances, and perhaps in the long run some clearer ways of determining whether assisted reproduction carries medical risks for IVF children.

The irony of this is not lost on stem cell research advocates.

Critics of the field have long maintained that embryonic stem cell work is morally wrong because it typically requires the destruction of embryos to produce the stem cells. Now, it seems an argument could be made that one of the first clear-cut results of the stem cell work may be a few more babies being born than might otherwise have been the case.

That doesn't eliminate the moral concern, of course, because critics object to any deliberate destruction of one life in order to save another.

Still, "it's an interesting twist," said Dr. Claire Pomeroy, dean of the UC Davis School of Medicine in Sacramento, another member of the Prop. 71 oversight board.